Structure of a Burkholderia pseudomallei Trimeric Autotransporter Adhesin Head

Abstract

BackgroundPathogenic bacteria adhere to the host cell surface using a family of outer membrane proteins called Trimeric Autotransporter Adhesins (TAAs). Although TAAs are highly divergent in sequence and domain structure, they are all conceptually comprised of a C-terminal membrane anchoring domain and an N-terminal passenger domain. Passenger domains consist of a secretion sequence, a head region that facilitates binding to the host cell surface, and a stalk region.Methodology/Principal FindingsPathogenic species of Burkholderia contain an overabundance of TAAs, some of which have been shown to elicit an immune response in the host. To understand the structural basis for host cell adhesion, we solved a 1.35 Å resolution crystal structure of a BpaA TAA head domain from Burkholderia pseudomallei, the pathogen that causes melioidosis. The structure reveals a novel fold of an intricately intertwined trimer. The BpaA head is composed of structural elements that have been observed in other TAA head structures as well as several elements of previously unknown structure predicted from low sequence homology between TAAs. These elements are typically up to 40 amino acids long and are not domains, but rather modular structural elements that may be duplicated or omitted through evolution, creating molecular diversity among TAAs.Conclusions/SignificanceThe modular nature of BpaA, as demonstrated by its head domain crystal structure, and of TAAs in general provides insights into evolution of pathogen-host adhesion and may provide an avenue for diagnostics.

Complete fiber structures of complex trimeric autotransporter adhesins conserved in enterobacteria

“…3C), a HIM3 forms additional interactions, folding tightly around the succeeding neck domain. Comparable interaction patterns can be observed for a HIM2 in the partial Burkholderia pseudomallei TAA head structure 3LAA (17) (Fig. 3F).…”

“…In a superposition with the only other available FGG structure in 3LAA (ref. 17; Fig. 7A), the structures only deviate in the loops of the β-hairpins where they differ in length.…”

“…Several head structures, from YadA (15), Hia (16), BadA (13), and BpaA (17), revealed different trimeric complexes with novel folds. Partial stalk structures from UspA1 (18), SadA (19), and YadA (20) substantiated earlier predictions that coiled coils are the dominant structural motif of TAA stalks, albeit sometimes with noncanonical properties such as unusual periodicities or ion binding sites in their core.…”

Functional Characterization of Burkholderia pseudomallei Trimeric Autotransporters

“…BoaA and BoaB have been reported to function as adhesins in vitro and to contribute to B. pseudomallei replication inside macrophage-like cells (21). A portion of the passenger domain of a third AT protein, encoded by bpaA, has been crystallized, and the structure of its tightly woven trimeric head region resembles that of other trimeric ATs, including YadA, Hia, and BadA from Bartonella henselae (31). In this study, we investigated eight B. pseudomallei trimeric ATs and evaluated their roles in adherence, invasion, and plaque formation in vitro.…”

Autotransporter proteins of Uropathogenic Escherichia coli: regulation, characterisation and the role of periplasmic proteins in their expression

“…Interestingly, the EibD head and stalk structure revealed the stalk to coil in a left-handed direction from the β-barrel structure, and then switch to a right-handed-coil at approximately halfway (Leo et al, 2011). Crystal structures have also been solved for partial domains of other Gram-negative trimeric AT proteins, including the Yersinia adhesion YadA (Nummelin et al, 2004, Alvarez et al, 2010, Hia (Meng et al, 2006b, Yeo et al, 2004, UspA1 (Conners et al, 2008), SadA (Hartmann et al, 2009), BadA (Szczesny et al, 2008) and BpA (Edwards et al, 2010).…”